{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:03:58Z","timestamp":1789963438017,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study assessed the preclinical and clinical pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of ribupatide (HRS9531), a novel dual agonist of glucagon\u2010like peptide\u20101 (GLP\u20101) and glucose\u2010dependent insulinotropic polypeptide (GIP) receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Preclinical assessments of ribupatide included in\u00a0vitro functional receptor potency assays, PK evaluations in Sprague\u2013Dawley (SD) rats and cynomolgus monkeys and PD assessments in diet\u2010induced obese (DIO) mice. The Phase 1 study comprised single\u2010ascending dose (SAD; 0.1, 0.3, 0.9, 2.7, 5.4 and 8.1\u2009mg) and multiple\u2010ascending dose (MAD; 0.9, 2.7 and 5.4\u2009mg [2.7\/2.7\/4.0\/5.4\u2009mg]) parts. In the MAD part, ribupatide or placebo was administered subcutaneously once weekly for 4\u2009weeks. The primary endpoints were safety and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ribupatide is a chemically synthesised polypeptide that activates both GLP\u20101 and GIP receptor signalling pathways in\u00a0vitro. In SD rats and cynomolgus monkeys, ribupatide demonstrated good subcutaneous bioavailability. In DIO mice, it significantly reduced body weight and cumulative food intake over 28\u2009days compared with vehicle\u2010treated controls. These preclinical PK\/PD findings provided a rationale for clinical studies. A total of 90 healthy Chinese participants were randomised and received study treatment, of whom 87 (96.7%) completed the study. Ribupatide was well tolerated across all dose levels, with all treatment\u2010emergent adverse events (TEAEs) being mild\u2010to\u2010moderate in severity and no serious TEAEs or deaths reported. In the MAD, the mean half\u2010life was 7\u20138\u2009days across the dose range. Fasting plasma glucose decreased dose\u2010dependently after single and multiple dosing. After four weekly doses, mean weight change in ribupatide groups ranged from \u22124.3\u2009kg (\u22126.7%) to \u22127.7\u2009kg (\u22129.6%), compared with \u22121.2\u2009kg (\u22121.4%) in the placebo group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ribupatide exhibited a favourable safety and tolerability profile, along with PK properties consistent with once\u2010weekly administration. Its glucose\u2010lowering and weight\u2010loss effects support further clinical development for the treatment of type 2 diabetes mellitus and obesity.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      ClinicalTrials.gov identifier: NCT05152277.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71218","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:37:47Z","timestamp":1789961867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical and First\u2010In\u2010Human Evaluation of Ribupatide (\n                    <scp>HRS9531<\/scp>\n                    ), a Dual\n                    <scp>GLP<\/scp>\n                    \u20101\/\n                    <scp>GIP<\/scp>\n                    Receptor Agonist"],"prefix":"10.1111","author":[{"given":"Kun","family":"He","sequence":"first","affiliation":[{"name":"Department of Clinical Research Centre Central Hospital Affiliated to Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Centre Central Hospital Affiliated to Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Centre Central Hospital Affiliated to Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Global Research and Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhou","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Peptide Chemistry Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Peptide Chemistry Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research &amp; Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Clinical Research &amp; Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhi","sequence":"additional","affiliation":[{"name":"Nonclinical Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nonclinical Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Sheng","sequence":"additional","affiliation":[{"name":"Clinical Research &amp; Development Jiangsu Hengrui Pharmaceuticals Co. Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3915-9616","authenticated-orcid":false,"given":"Qing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Centre Central Hospital Affiliated to Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41573-025-01183-8","article-title":"GLP\u20101\u2010Based Therapies for Diabetes, Obesity and Beyond","volume":"24","author":"Drucker D. 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